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Function: _error_handler
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Filename: controllers/Detail.php
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Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-inducible constitutively active form of Rac1 (CA-Rac1) in podocytes. Regardless of the copy number, proteinuria occurred rapidly within five days, and the histology resembled minimal change disease. The degree and severity of proteinuria were dependent on the transgene copy number. Upon doxycycline withdrawal, proteinuria resolved completely (one copy) or nearly completely (two copy). After one month of doxycycline treatment, two-copy mice developed glomerulosclerosis that resembled focal segmental glomerulosclerosis (FSGS) with urinary shedding of transgene-expressing podocytes. p38 MAPK was activated in podocytes upon CA-Rac1 induction while a p38 inhibitor attenuated proteinuria, podocyte loss, and glomerulosclerosis. Mechanistically, activation of Rac1 in cultured mouse podocytes reduced adhesiveness to laminin and induced redistribution of β1 integrin, and both were partially reversed by the p38 inhibitor. Activation of Rac1 in podocytes was also seen in kidney biopsies from patients with minimal change disease and idiopathic FSGS by immunofluorescence while sera from the same patients activated Rac1 in cultured human podocytes. Thus, activation of Rac1 in podocytes causes a spectrum of disease ranging from minimal change disease to FSGS, due to podocyte detachment from the glomerular basement membrane that is partially dependent on p38 MAPK.
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http://dx.doi.org/10.1016/j.kint.2017.03.010 | DOI Listing |
Antimicrob Resist Infect Control
December 2024
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Infection prevention and control (IPC) programs form the basis of minimizing spread of pathogens in the healthcare setting and beyond. The COVID-19 pandemic amplified the demand for IPC. However, the environmental impact of IPC practices has yet to be addressed and attempts to quantify its climate implications have been sparse.
View Article and Find Full Text PDFBMJ Open
December 2024
Department of Primary Care and Public Health, School of Public Health, Imperial College London Faculty of Medicine, London, UK
Objectives: We sought to review studies that examine healthcare professionals' and students' knowledge, attitudes and practices (KAP) regarding medication disposal. We also explore recommendations and barriers related to appropriate medication disposal.
Design: A systematic review was conducted that adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Lung India
January 2025
Department of Pulmonary and Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India.
Background And Objective: Obstructive sleep apnea (OSA) is a common condition, featured by repetitive upper airway collapse during sleep manifested with poor quality of life and co-morbidities. Although continuous positive airway pressure (CPAP) is the recommended therapy, lack of patient compliance and persistent symptoms often preclude its success. The present study evaluates the effect of acetazolamide in combination with CPAP, and compares this treatment strategy to single therapy using CPAP in moderate to severe OSA.
View Article and Find Full Text PDFInt J Biometeorol
December 2024
Department of Ecosystem Science and Management, University of Wyoming, Laramie, WY, 82071, USA.
For non-hibernating species within temperate climates, survival during severe winter weather often depends on individuals' behavioral response and available refugia. Identifying refugia habitat that sustains populations during adverse winter conditions can be difficult and complex. This study provides an example of how modeled, biologically relevant snow and weather information can help identify important relationships between habitat selection and dynamic winter landscapes using greater sage-grouse (Centrocercus urophasianus, hereafter "sage-grouse") as a model species.
View Article and Find Full Text PDFSoc Sci Med
December 2024
College of Management and Economics, Tianjin University, Tianjin, 300072, China; Center for Social Science Survey and Data, Tianjin University, Tianjin, 300072, China. Electronic address:
This study uses panel data from the 2011, 2013, 2015, 2018, and 2020 China Health and Retirement Longitudinal Study to examine the labor supply effects of spousal disability in later life. Employing a staggered difference-in-differences strategy, we provide causal evidence of gender-specific impacts, with a significant and enduring negative effect on female employment lasting over eight years, in contrast to minimal changes for males. The negative effect on female employment is particularly pronounced among low-educated individuals, those with agricultural hukou, and those influenced by stronger Confucian cultural norms.
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